Carcinogens from diverse chemical classes induce neoplastic transformation of guinea pig fetal cells in culture. The transition to the neoplastic state often occurs in a stepwise manner. Morphological transformation frequently precedes neoplastic transformation, the ability of the cells to produce progressively growing tumors in syngeneic guinea pigs, by several months after carcinogen treatment. Alterations in plating efficiency, growth rate, and chromosome number and structure are not necessary for the development of neoplastic transformation. The ability of transformed cells to grow as colonies in agar, susceptibility of the cells to cytotoxic effects of lymphotoxin, intradermal skin reactivity of transformed cells in nonimmune guina pigs, and secretion of large amounts of plasminogen activator are characteristics that correlate well with neoplastic transformation. These cell properties are useful indicators of the tumorigenic potential of guinea pig cells transformed by chemical carcinogens and for study of somatic cell alterations essential for the development of the neoplastic state.